4-(methylthio)butanal fragrance modifier

ABSTRACT

Processes and compositions for altering the organoleptic properties of consumable materials utilizing 4-(methylthio)butane derivatives having the formula   WHEREIN X is hydrogen and Y is a carbonyl oxygen; X is hydroxy and Y is two hydrogen atoms or a carbonyl oxygen; or X is lower alkoxy and Y is (a) carbonyl oxygen or (b) hydrogen and lower alkoxy, together with novel compositions to effectuate such methods and processes for producing such derivatives.

United States Patent [191 Pittet et al. Sept. 9, 1975 [54]4-(METHYLTHIO)BUTANAL FRAGRANCE 3,419,617 12/1968 Doss 260/601 R M I3,522,293 7/1970 Harris 260/481 R Inventors: Alan 0. Pittet, AtlanticHighlands;

John V. Pascale, Jackson, both of N.J.; Stuart Patton, State College,Pa.; Michael H. Brodnitz, Matawan, NJ.

International Flavors & Fragrances Inc., New York, NY.

Filed: Mar. 1, 1974 Appl. No.: 447,661

Related U.S. Application Data Division of Ser. No. 301,524, Oct. 27,1972, Pat. No. 3,870,800.

Assignee:

U.S. Cl 252/522; 260/455; 260/48] R; 260/601 R Int. Cl. A61K 7/00; C1 1B9/00 Field of Search 252/522; 260/601 R, 455, 260/481 R References CitedUNITED STATES PATENTS 10/1967 Doss 260/455 Primary ExaminerVeronicaOKeefe Attorney, Agent, or FirmBrooks Haidt Haffner & DelahuntyProcesses and compositions for altering the organoleptic properties ofconsumable materials utilizing 4-(methylthio)butane derivatives havingthe formula ABSTRACT 1 Claim, N0 Drawings 4-(METHYLTHIO)BUTANALFRAGRANCE MODIFIER This is a division of application Ser. No. 301,524,filed Oct. 27, 1972 now US. Pat. No. 3,890,800.

BACKGROUND OF THE INVENTION The present invention relates to novelmethods of altering the organoleptic properties of consumable materialssuch as foods and the like, and to compositions for effecting suchmethods and processes for'the production of a number of derivatives of(methylthio)butane.

Various 4-(methylthio)butyl derivatives are known. Thus,4-(methylthio)butanol is shown in Chemical Abstracts 55, 1 l9 1;4-(methylthio)butyric acid, in Chemical Abstracts 44, 6943; the diethylacetal of 4-(methylthio)butyraldehyde, in Chemical Abstracts 54, 9772;and the same or similar materials are also shown in Chemical Abstracts55, 20927; 70, 115563; and 68, 53398. While some of the materials havebeen suggested for use as plasticizers, there has been no suggestion ofsuch methylthiobutyl derivatives for use in altering tastes or aromas,nor are tastes or aromas suggested.

Methional, 3-(methylthio)propionaldehyde, has been said to be widelydistributed in common natural foods, and it is said to be used in anumber of imitation flavors, mainly cheese, meat and fruit flavors aswell as in spice blends and concentrated soup flavors. It is said inArctander, Perfume and Flavor Chemicals, that it has a powerful anddiffusive onionand meat-like odor. The taste in concentrations of lessthan ppm is said to be pleasant warm meator soup-like with a bite orpungency at higher concentrations. It has also been said to beproductive of potato flavor under certain conditions of use. Methionol,3-(methylthio)propanol,is said to have been found in soysauce and isstated in Arctander, loc.cit., to have a powerful and sweet soupormeat-like odor and flavor.

The reduction of esters to aldehydes with diisobutyl aluminum hydridehas been shown in Tetrahedrom Letters 14, 619, and the use of a materialcomprising sodium dihydro bis(2-methoxyethoxy) aluminate has beensuggested as a reducing agent to reduce carbonyl compounds to alcohols.Chemical Abstracts 55, 20927 shows a process for the production of4-(methylthio)- butyraldehyde diacetal from the reaction of the 1,1diethoxy-3-butane with methyl mercaptan in the presence of theultraviolet radiation or a mercuric oxide catalyst. Other syntheses ofmaterials are shown in Chemical Abstracts 47, 11227; 47, 1723; 58,11211; 50, 16785; 45, 10198; 44, 9919; 57, 12303; 67, 43362; 55, 25829;57, 7289; and 76, 2516.

THE INVENTION -contemplate the addition of a small but effective amountof at least one 4-(methylthio)butane derivative having the formulawherein X is hydrogen, and Y is a carbonyl oxygen; X is hydroxy and Y isa carbonyl oxygen or two hydrogen atoms; or X is lower alkoxy and Y is(a) carbonyl oxygen or (b) lower alkosy and hydrogen, sufficient toalter the organoleptic properties of the consumable material. Theinvention further contemplates novel processes for the production ofcertain (methylthio)butyl derivatives and compositions suitable for usein altering organoleptic properties.

The alkoxy groups encompassed by X and Y in the foregoing formula arepreferably lower alkoxy groups containing from one to about three carbonatoms. In certain preferred emodiments of the invention describedherein, the preferred alkosy groups are methoxy and ethoxy. It will beappreciated by those skilled in the art from the present descriptionthat certain preferred compounds for use herein are provided accordingto the foregoing formula when Y is carbonyl and X is hydrogen, hydroxy,methoxy or ethoxy; when Y is two hydrogen atoms and X is hydroxy; andwhen Y is hydrogen and methoxy or ethoxy and X is methoxy or ethoxy.

Thus, the present invention. contemplates the use of4-(methylthio)butanol having a metallic character to provide amushroom-like, tomato-like, vegetable-like, cheesy, fruity taste;4-(methylthio)butanol to impart a metallic, tomatopotato, fish oil-like,cabbage taste; 4-(methylthio)butyric acid having a metallic, tin can,tomato-like odor and green vegetable flavor with metallic note; themethyl ester of 4-(methylthio)butyric acid to provide a sweet, roasted,nut-like, dairy, vegetable-like taste; the ethyl ester of4-(methylthio)buryric acid to provide sweet metallic fruity, cheesy,onion-like flavor and aroma character; and the diethylacetal of4-(methylthio)-butyraldehyde, also known asl,ldiethoxy-4-(methylthio)-butane, to provide a mushroom, heated onion.flavor with green, sweet tomator with onion and garlic fragrancenuances.

It will be appreciated from the present disclosure that the(methylthio)butane derivatives and mixtures thereof according to thepresent invention can be used to alter, vary, fortify, modify, enhance,or otherwise improve the flavor and/or aroma of a wide variety ofmaterials which are ingested, consumed, or otherwise organolepticallysensed. The term alter in its various forms will be understood herein tomean the supplying or imparting a flavor character or note to anotherwise bland, relatively tasteless substance, or augmenting anexisting flavor characteristic where the natural flavor is deficient insome regard, or supplementing the existing flavor or aroma impression tomodify the organoleptic character.

Such 4(methylthio)butane derivatives are accordingly useful in flavoringcompositins. Such flavoring compositions are herein taken to mean thosewhich contribute a part of the overall flavor impression bysupplementing or fortifying a natural or artifical flavor in a material,as well as those which supply substantially all the flavor and/or aromacharacter to a consumable article.

The term foodstuff as used herein includes both solid and liquidingestible materials for man or animals, which materials usually do, butneed not, have nutritional value. Thus, foodstuffs includes meats,gravies, soups, convenience foods, malt and other alcoholic ornon-alcoholic beverages, milk and dairy products, nut butters such aspeanut butter and other spreads, seafoods including fish, crustanceans,mollusks and the like, candies, breakfast foods, baked goods,vegetables, cereals, soft drinks, snack foods, dog and eat foods, otherveterinary products, and the like.

The term tobacco will be understood herein to mean natural products suchas, for example, burley, Turkish tobacco, Maryland tobacco, flue-curedtobacco and the like including tobacco-like or tobaccobased productssuch as reconstituted or homogenized leaf and the like, as well astobacco substitutes intended to replace natural tobacco, such as lettuceand cabbage leaves the the like. The tobaccos and tobacco productsinclude those designed or used for smoking such as in cigarette, cigar,and pipe tobacco, as well as such as snuff, chewing tobacco, and thelike.

When the 4-(methylthio)butane derivatives according to this inventionare used in a flavoring composition, they can be combined withconventional flavoring materials or adjuvants. Such as co-ingredients orflavoring adjuvants are well known in the art for such use and have beenextensively described in the literature. Apart from the requirement thatany such adjuvant material be ingestibly acceptable, and thus non-toxicor otherwise non-deleterious, conventional materials can be used andbroadly include other flavor materials, vehicles, stabilizers,thickeners, surface active agents, conditions, and flavor intensifiers.

Such conventional flavoring material include saturated, unsaturated,fatty and amino acids; alcohols, including primary and secondaryalcohols; esters carbonyl compounds, including ketones and aldehydes;lactones; cyclic organic materials including benzene derivatives,alicyclics, heterocyclics such as furans, thiazoles, thiazolidines,pyridines, pyrazines and the like; other sulfur-containing materialsincluding thiols, sulfides, disulfides and the like; proteins; lipids;carbohydrates; so-called flavor potentiators such as monosodiumglutamate, guanylates, and inosinates; natural flavoring materials suchas cocoa, vanilla, and caramel; essential oils and extracts such asanise oil, clove oil and the like; artificial flavoring materials suchas vanillin; and the like.

It has been found in certain preferred embodiments that variousadjuvants are particularly suited for use with various(methylthio)butane derivatives according to the present invention. Thus,4(methylthio)butanol at levels of 0.1 to 2 ppm has a considerableadvantage in enhancing the flavor of vegetable and mushroom products andin overcoming flour and starch notes in, for example, soups. The4-(methylthio)butanal has similar utility. In tobacco formulations, thebutyric esters and particularly the ethyl ester of 4-(methylthio)-butyric acid has the advantage of providing excellent fruit flavorsWhile permitting the use of high levels of acetaldehyde, levels as muchas tenfold those which can otherwise be used.

In view of the utility of compounds according to the present inventionfor tomato, potato, cheese, and mushroom and for enhancing meat flavors,it is preferred in certain embodiments that the 4(methylthio)- butanederivative or derivatives be combined with one or more adjuvants such asZ-isobutylthizole, 2-isobutyl- 3-methoxypyrazine, maltol,4-methyl-5-thiazolol, 2,4- pentadienal,4-hydroxy-2,5-dimethyl-2H-furan-3-one, 2-methyl-3-furanthiol,2-ethyl-3-acethylpyrazine, or allyl caproate.

Stabilizers include preservatives such as sodium chloride and the like,antioxidants such as calcium and sodium ascorbate, ascorbic acid,butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate andthe like, sequestrants such as citric acid, EDTA, phosphates, and thelike.

Thickeners include carriers, binders, protective colloids, suspendingagents, emulsifiers and the like, such as agar-agar, carrageenan,cellulose and cellulose derivatives such as carboxymethyl cellulose andmethyl cellulose, and the like, and other proteinaceous materials,lipids, carbohydrates, starches and pectins.

Surface active agents include emulsifying agents such as monoand/ordiglycerides of fatty acids including capric acid, caprylic acid,palmitic acid, myristic acid, oleic acid, and the like, lecithin,defoaming and flavordispersing agents such as sorbitan monostearate,potassium stearate, hydrogenated tallow alcohol, and the like.

Conditioners include compounds such as bleaching and maturing agentssuch as benzoyl peroxide, calcium peroxide, hydroben peroxide and thelike; starch modifiers such as peracetic acid, sodium chlorite, sodiumhypochlorite, propylene oxide, succinic anhydride and the like, buffersand neutralizing agents such as sodium acetate, ammonium bicarbonate,ammonium phosphate, citric acid, lactic acid, vinegar and the like;colorants such as carminic acid, cochineal, turmeric curcumin, approvedfood and drug dyes, and the like; firming agents such as aluminum sodiumsulfate, calcium chloride and calcium gluconate; texturizers; anticakingagents such as aluminum calcium sulfate and tribasic calcium phosphate;enzymes; yeast foods such as calcium lactate and calcium sulfate;nutrient supplements such as iron salts including ferric phosphate,ferric pyrophosphate, ferrous gluconate adn the like, riboflavin,vitamins, zinc sources such as zinc chloride, zinc sulfate, and thelike.

The l-(methylthio(butane derivatives, or the compositions incorporatingthem, as mentioned above, can be combined witn one or more vehicles orcarriers for adding them to the particular product. Vehicles can beedible or otherwise suitable materials such as ethyl alcohol, propyleneglycol, water, and the like. Carriers include materials such as gumarabic, carrageenan, other gums, and the like. The methylthiobutanecompounds can be incorporated with the carriers by conventional meanssuch as spray-drying, drum-drying, and the like. Such carriers can alsoinclude materials for coacervating the butane derivatives (and otherflavoring ingredients, as present) to provide encapsulated products.When the carrier is an emulsion, the flavoring composition can alsocontain emulsifiers such as monoand diglycerides of fatty acids and thelike. With these carriers or vehicles, the desired physical form of thecomposition can be prepared.

It will be understood by those skilled in the art that the 4-(methylthio)butanc derivatives according to the present invention can beadded to the materials to be flavored at any convenient point in theproduction of the finished product. Thus, when the derivatives are usedto alter or otherwise vary the flavor of the foodstuff, they can beadded in the original mixture, dough, emulsion, batter, or the likeprior to any cooking or heating operation. Alternatively, they can beadded at a later stage of processing if volatilization losses would beexcessive during the earlier processing.

When the derivatives areused to treat tobacco products for example, theadditive can be applied in a suit able manner, as by spraying, dipping,or otherwise. They can be applied during the casing or final spraytreatment of the tobacco, or they can be applied at some earlier stageof curing or preparation. The quantity of 4-(methylthio)-butanederivatives or mixtures thereof utilized should be sufficient to impartthe desired flavor characteristic to the product, but on the other hand,the use of an excessive amount of deriva-' tive is not only wasteful anduneconomical, butin some instances too large a quantity may unbalancethe flavor or other organoleptic properties of the product-consumed. Thequantity used will vary depending upon the ultimate foodstuff, tobaccoproduct, or other consumable product; the amount and type of flavorinitially present in the product; the further process or treatment stepsto which the product will be subjected; regional and other preferencefactors; the type of storage, if any, to which the product will besubjected; and the preconsumption treatment, such as baking, frying, andso on, given to the product by the ultimate consumer. Accordingly, theterminology effective amount and sufficient amount is understood in thecontext of the present invention to be quantitatively adequate to alterthe flavor of the foodstuff, tobacco, or other consumable material.

It is accordingly preferred that the ultimate compositions contain fromabout parts per million (ppm) to about 200 ppm of methylthiobutanederivative or derivatives. More particularly, in food compositions it isdesirable to use from about 0.01 ppm for enhancing flavors and incertain preferred embodiments of the invention, from about 1 to 25 ppmof the derivatives are included to add positive flavors to the finishedproduct. On the other hand, tobacco compositions can contain as littleas 0.01 ppm and as much as 200 ppm depending upon whether a cigarettetobacco, a pipe tobacco, a cigar tobacco, at chewing tobacco, or snuffis being prepared. All parts, proportions, percentages, and ratiosherein are by weight unless otherwise indicated.

The amount of methylthiobutyl material or materials to be utilized inflavoring compositions can be varied over a wide range depending uponthe particular quality to be added to the foodstuff, tobacco, or otherconsumable material. Thus, amounts of one or more derivatives accordingto the present invention from about 0.1 ppm up to 80 or 90 percent canbe incorporated in such compositions. it is generally found to bedesirable to include from about 0.1 ppm to about 0.1 percent of thederivatives in such compositions.

The (methylthio)butane derivatives of this invention are also usefulindividually or in admixtures as fragrances. They can be used tocontribute various fruity, woody, or floral fragrances. As olfactoryagents, the derivatives of this invention can be formulated into or usedas components of a perfume composition.

A perfume composition is composed of a small but effective amount of a'(methylthio)butane derivative according to this invention and anauxiliary perfume ingredient. including, for example, alcohols,aldehydes, ketones, nitriles, esters, and frequently hydrocarbons whichare admixed so that the combined odors of the individual componentsproduce a pleasant or desired fragrance. Such perfume compositionsusually contain (a) the main note or the bouquet or foundationstone ofthe composition; (b) modifiers which roundoff and accompany the mainnote; (0) fixatives which include odorous substances which lend aparticular note to the perfume throughout all stages of evaporation, andsubstances which retard evaporation, and (d) top'notes which are usuallylow-boiling fresh smelling materials.

In perfume compositions the individual component will contribute itsparticular olfactory characteristics, but the overall effect of theperfume composition will be the sum of the effect of each ingredient.Thus, the individual derivatives of this invention, or mixtures thereof,can be used to alter the aroma characteristics of a perfume composition,for example, by highlighting or moderating the olefactory reactioncontributed by another ingredient in the composition. 1

The amount of the compounds of this invention which will be effective inperfume compositions de pends on many factors, including the otheringredients, their amounts and the effects which are desired. It hasbeen found that perfume compositions containing as little as 0.2 percentof the compounds of this invention, or even less, can be used to imparta scent odor to soaps, cosmetics, and the other products. The amountemployed can range up to five percent or higher of the fragrancecomponents and will depend on consider-.

ations of cost, nature of the end product, the effect desired on thefinished product and the particular fragrance sought.

The derivatives of this invention can be used alone or in perfumecomposition as an olfactory component in detergents and soaps; spaceodorants and deodorants; perfumes; colognes; toilet waters; bathpreparations such as bath oil and bath salts; hair preparations such aslacquers, brilliantines, pomades, and shampoos; cosmetic preparationssuch as creams, deodorants, hand lotions, and sun screens; powders suchas talcs, dusting powders, face powder, and the like. When used as anolfactory component of a perfumed article, as little as ppm of one ormore of the preferred 4 -(methylthio)-butane derivatives will suffice toimpart a floral, geranium odor character. Generally, no more than 0.5percent is required in the perfume composition.

In addition, the perfume composition or fragrance composition cancontain a vehicle or carrier for the 4-methylthio)butane derivativesalone or with other ingredients. The vehicle can be a liquid such asalcohol, glycol, or the like. The carrier can be an absorbent solid suchas gum or components for encapsulating the composition.

It will thus be apparent that the derivatives according to the presentinvention can be utilized to alter the sensory properties, particularlyorganoleptic properties such as flavor and/or fragrance of a widevariety of consumable materials.

The present invention further provides novel pro cesses for thepreparation of certain compounds used herein. The 4-(methylthio )butanolcan be obtained from the diethoxybutene by reaction with methyl mercaptan and subsequent acid hydrolysis. The acetal starting material isprepared by reacting triethyl orthoformate with allyl magnesiumchloride. The acetal so obtained is then admixed with methyl mercaptanand exposed to ultra-violet radiation. This provides 4-(methylthio)butyraldehyde diacetal which is then reacted with dilute acidto obtain 4-(methylthio)butanal.

The ultra-violet irradiation is carried out at temperatures of fromabout -40 to about 40C in order to give good completenesses with controlof the reaction velocity. The reaction can be carried out underatmospheric or super-atmospheric conditions, and atmospheric pressure ispreferred. The ratio of mercaptan to acetal can vary over a range offrom several times the molar quantity of mercaptan to several times themolar quantity of acetal. In certain desired embodiments of theinvention, the amounts of the two reactants range from about equimolarto a 20 molar percent excess of mercaptan.

If desired, the reaction can be carried out in the presence of areaction vehicle, but it is usually desirable to use little or noreaction vehicle. The time of reaction will vary depending upon thecompleteness desired, the temperature, the pressure, the ratio ofreactants and like variables. With the radiation intensities normallyavailable in the laboratory and small-scale production, reaction timesof 30 minutes to four hours are utilized.

After the thio derivative has been formed, and if desired purified asherein described, it is treated with a dilute acid to provide thealdehyde. A wide variety of acid materials can be used, and mineralacids such as phosphoric, hydrochloric and sulfuric are desirable.Particularly preferred is concentrated sulfuric acid which has beendiluted with from about four to about 25 times its volume of water.

The treatment to provide the aldehyde is carried out at tempertures offrom avout to about 50C, and temperatures on the order of 25C arepreferred. At such temperatures the reaction is carried out in from 1 to8 hours.

The intermediate and/or final products obtained can be purified orisolated by conventional purification after appropriate washing,neutralizing and/or drying as appropriate. Thus, such products can bepurified and- /or isolated by distillation, steam distillation, vacuumdistillation, extraction, crystallization, preparative chromatographictechniques, and the like.

The 4-(methylthio)butanal utilized herein can also be prepared by adirect reduction of a 4-(methylthio)- butyric acid ester. Organometallichydrides are used to provide the desired aldehyde as the final product.Examples of preferred reducing agents are dialkyl aluminum hydrides suchas diisobutyl aluminum hydride and bis-(alkoxyalkyl) dihydro aluminatesuch as bis- (methoxyethoxy) dihydro aluminate. This last material isavailable under the trade name RED-AL from Aldrich Chemical Company,Milwaukee, Wisconsin, USA.

The reduction directly to provide the aldehyde is carried out atrelatively low tempertures on the order of 1 00 to l0C. In certainpreferred embodiments, dry ice-solvent baths are used and the preferredtemperatures are from about 70C to about 50C. The reaction is carriedout for from 1 to about hours to provide good reaction completeness. Itis generally desirable to gradually raise the temperature to provide forcompleteness of the reaction while at the same time providing goodcontrol thereof.

It is usually desirable to carry out the reaction in an inert vehiclewhich moderates the course of the reaction. Such a reaction vehicle isone which will not be reduced by, or otherwise react with, the materialspresem and which is liquid at the relatively low temperatures utilized.It has been found desirable to use a vehicle in which the reactants aresoluble. Thus, suitable reaction vehicles include ethers such as diethylether,

liquid hydrocarbons such as hexane and the like, aromatic hydrocarbonssuch as a benzene-diethyl ether mixture, toluene and the like, andsimilar materials.

This reaction can be carried out over a range of pressures fromatmospheric to super-atmospheric, but it is generally preferred toconduct the reaction at C. It is also desirable to exclude moisturerigorously from the reaction mixture and it can accordingly bebeneficial to carry out the reaction under a blanket of inert gas suchas nitrogen. After the reaction is completed, the aldehyde productproduced is separated from the by-products and isolated and/or purifiedas set forth above.

The following examples are given to illustrate embodiments of theinvention as it is presently preferred to practice it. It will beunderstood that these examples are illustrative, and the invention isnot to be considered as restricted thereto except as indicated in theappended claims.

EXAMPLE 1 Preparation of Ethyl 4-(Methylthio)butyrate A 500 ml flaskequipped with mechanical stirrer, thermometer, reflux condenser, anddropping funnel, is charged with 500 ml of ethyl alcohol and 25 g ofsodium spheres. The alcohol is distilled into a second three-neck, 500ml flask equipped with magnetic stirrer, dry ice condenser, and calciumchloride drying tube. The second flask containing the distilled alcoholis charged with 14.4 g (0.625 moles) of pure freshly cut sodium, and31.2 g (0.65 moles) of methylmercaptan is distilled into the flask.

The mixture so obtained is transferred to a dropping funnel on another500 ml flask containing 68.3 (0.5 moles) of methyl 4-chloro-butyrate.The mercaptide solution is dropped into the flask while maintaining atemperature of 20C. When the reaction is completed, the liquid isfiltered and the ethanol is removed on a rotary evaporator. The slurryremaining after evaporation is added to 200 ml of ethyl ether, and thisis followed by the addition of 200 ml of water. The aqueous layer isextracted with ethyl ether and combined with the other ether layer, andthe combined layers are ex tracted with water until neutral.

The 50 g of ethyl 4-(methylthio)butyrate obtained boils at 7475C and 13mm Hg.

EXAMPLE II Preparation of 4-(Methylthio)butanal A three-neck 500 mlflask equipped with a mechanical stirrer, dropping funnel, andthermometer, and flushed with nitrogen, is charged with 16.8 g (u.l04moles) of ethyl 4-(methylthio)butyrate and 150 ml of ethyl ether. Theflask contents are cooled to 70C and 15 ml of 70 percent solution ofsodium dihydro bis (methoxyethoxy) aluminate in benzene mixed with 25 mlof ethyl other is added during a 20-minute period. The reaction mixtureis maintained at 70C for 6 hours.

Thereafter, ml of sulfuric acid diluted with five parts by volume ofwater is added during a 20-minute period. The temperature is allowed torise to Ol0C. The lower aqueous layer is separated from the ether andextracted thrice with l()() ml portions of ether.

The ether extracts are combined and washed with 20 ml of 5 percentaqueous sodium carbonate solution.

sulfate and filtered, and the ether is then removed on a rotaryevaporator.

The remaining organic material is distilled to obtain4-(methylthio)butane boiling at 9699C and 26 mm Hg.

EXAMPLE Ill Preparation of Methyl 4-(Methylthio)butyrate The procedureof Example 1 is repeated utilizing 73.75 g (0.625 moles) of sodiummethoxide, 31.2 g

(0.65 moles) of methyl mercaptan and 68.3 g (0.5 moles) of methyl 44ghlbrobutyrate. The methyl 4-(methylthio)butyrate 1% obtained in theamount of 29 g having a boiling point of 86C at mm Hg. The

1 product is over 96 percent pure, and the structure is confirmed bymass spectroscopy.

EXAMPLE IV Preparation of 4-(Methylthio)butanol EXAMPLE V Preparation ofMethyl 4-(Methylthio)butyrate A 500 ml three-neck flask equipped withmechanical stirrer, dry ice condenser, and calcium chloride drying tubeis charged with 350 ml of absolute methanol and cooled to 10C beforeadding 73.75 g (0.625 moles) of sodium methoxide. The methoxide is addedin batches during 1 hour while the temperature is maintained at C. Anadditional hour of stirring is necessary to effect complete solution.

A 250 ml flask is charged with 31.2 g (0.65 moles) of chilled methylmercaptan, and the mercaptan is allowed to distill into theaforementioned flask during a one-half hour period. The mixture soobtained is transferred to a dropping funnel on a 500 ml three-neckflask equipped with mechanical stirrer, thermometer, reflux condenser,and dropping funnel. This last flask is charged with 68.3 g (0.5 moles)of methyl 4- chlorobutyrate. The mercaptide solution is added duringone-half hour while the temperature is maintained at 20C. The mixture isthen stirred for an additional hour as the temperature rises to 35C.

The solids are then removed from the reaction mixture by suctionfiltration, and the remaining solution is placed in a rotary evaporatorto remove the methanol. The liquid-solid mixture is treated with 200 mlof ether and 200 ml of water.

The two phases are separated, the aqueous layer is extracted thrice withether, and the ether layers are combined. The combined layers areextracted with 20 ml portions of water until neutral. The solvent isremoved on a rotary evaporator and a two-phase system is obtained. Theorganic material is dissolved in 100 ml of ether, the layers areseparated, and the ether is removed to obtain 43 g of methyl4-(methylthio)butyrate. Gas-liquid chromatography (GLC) shows theproduct to be substantially 100 percent pure.

EXAMPLE VI Preparation of 4-(Methylthio)butanal A one-liter, three-neckround bottom flask equipped with a mechanical stirrer, thermometer,nitrogen blanket and dropping funnel is charged with 22.2 g (0.15 moles)of methyl 4-(methylthio)butyrate in 225 ml of ethyl ether and cooled toC with a dry ice-acetone bath. A 70 percent solution in benzene ofsodium dihydro bis-(methoxyethoxy) aluminate in the amount of 30 ml inml ethyl ether is added to the flask contents during /2 hour while thetemperature is maintained at 70C to 65C.

The reaction mixture is then stirred for three addtional hours, afterwhich time 500 ml of aqueous sulfuric acid diluted 1:1 with water isadded. The addition begins at 70C and the temperature at the end of theacid addition is -l0C. The flask contents are charged to a one-literseparatory funnel, the upper organic phase is separated, and the loweraqueous phase is extracted thrice with ether. The ether extract iscombined with the organic phase, and the combined layers are extractedwith 20 ml to 5 percent aqueous sodium carbonate. The ether is thendried and stripped on a rotary evaporator. The remaining material isdistilled to provide about 5 g of 4-(methyltlhio)-butanal as a liquidboiling at 87C and 25 mm Hg.

EXAMPLE V11 Preparation of Methyl 4-(Methylthio)butyrate A one-liter,three-neck flask equipped with mechanical stirrer, therometer, dry icecondenser, and drying tube, is charged with 700 ml of methanol andcooled to 15C with a dry ice-isopropanol bath. After the methanol ischilled, 141.6 g (1.2 moles) of sodium methoxide is added during V2 hourwhile the temperature is maintained at 20C or less. A 500 ml flask ischarged with 62.4 g (1.3 moles) of methyl .mercaptan and attached to thereaction flask, whereafter the methyl mercaptan is distilled into thereaction flask during /2 hour.

The mixture so obtained is transferred to one-liter dropping funnel andthe funnel is placed on a two-liter, three-neck flask equipped withthermometer, mechanical stirrer, and drying tube and containing 136.6 g(1.0 moles) of methyl 4 -chlorobutyrate and 100 ml of methanol. Thesodium methyl mercaptide solution in the dropping funnel is added to thebutyrate solution during one-half hour while the reaction temperature ismaintained at from 15 to 20c. After addition of mer captide solution iscompleted the mixture is allowed to reach 35C by the exothermic reactionduring 1 hour while the mixture is stirred.

After the additional exothermic period the methanol is removed by rotaryevaporation, the solid-liquid mixture remaining is dissolved in 600 mlof water, and the solution so obtained is extracted with ether. Theether extract is dried and evaporated to provide 40 g of 95.1 percentpure methyl 4(methylthio)butyrate as a liquid boiling at 92 94C and 17mm Hg.

EXAMPLE 'Vlll Preparation of Methyl 4-(Methylthio)butyratc A two-liter,three'neck flask equipped with mechanical stirrer, thermometer, dry icecondenser, and calcium sulfate drying tube is charged with oneliter ofmethanol cooled to 20C and then with 97.9 g (0.83 moles) of sodiummethoxide during /2 hour while the temperature is maintained at 20C bycooling with dry (ice-isopropanol) bath. Then 48 g of methyl mercaptanis distilled into the sodium methoxide-methanol mixture without cooling.

The resulting clear solution is charged to a one-liter dropping funnelon a twoliter, three-neck flask equipped with a mechanical stirrer,thermometer, and calcium sulfate drying tube, the one-liter flaskcontaining 1 13.6 g (0.83 moles) of methyl 4-chlorobutyrate in 100 ml ofmethanol. The sodium methyl mercaptide solution in the dropping funnelis added during /2 hour while the temperature of 20C is maintained withslight cooling. When addition of the mercaptide solution is completedthe exothermic reaction is allowed to warm the flask contents to 30C.The flask contents are then heated to 60C over /2 hour and cooled to30C. The sodium chloride produced in the reaction is filtered off bysuction, and the methanol is removed by rotary evaporation. Theremaining liquid-solid mixture is extracted twice with 400 ml of etherand once with 200 ml of water. The ether is dried and removed.

The remaining liquid is distilled to obtain 58 g of methyl4-(methylthio)butyrate having a boiling point of 8485C at 15 mm Hg and arefractive index of 1.4647 at 25C.

EXAMPLE IX Preparation of 4-(Methylthio)butanal A three-liter,three-neck flask equipped with mechanical stirrer, thermometer, droppingfunnel, and nitrogen blanket, is charged with 74 g (0.5 moles) of methyl4-(methylthio)-butyrate in 100 ml of ethyl ether and cooled to -70C. 100milliliters of a 70 percent benzene solution of sodium dihydrobis-(methoxyethosy) aluminate in 100 ml of ethyl ether is added duringV2 hour while the solution is maintained at 70C, and the solution isthen stirred at -70C for four hours after the 100 ml (0.5 moles) ofaluminate has been added. Thereupon, one-liter of sulfuric acid diluted1:5 with water is slowly added while the temperature is raised from 70Cto lC.

The resulting mixture is charged to a four-liter separatory funnel, theupper organic phase is separated, and the lower aqueous phase isextracted thrice with 200 ml portions of ether. All of the organicphases are combined and extracted with 20 ml of 5 percent aqueous sodiumcarbonate. The ether is then dried and removed upon a rotary evaporator.

The remaining material is distilled to provide a 13 g portion containing78.5 percent of 4-(methylthio)- butanal product, 265 g of materialcontaining 51.5 percent product, and l g of material containing 14.8percent product.

EXAMPLE X Preparation of 1,1-Diethoxy-3-butene A l2-liter reaction flaskequipped with a reflux condenser, mechanical stirrer, dropping funnel, adrying tube and isopropanol cooling bath, is charged with 448 g ofmagnesium turnings and 0.5 liters of diethyl ether.

The reaction mass is stirred and exothermed to reflux, whereupon 5.5liters of deithyl ether and a solution of 1380 g of allyl chloride inthree liters of diethyl ether is added.

The addition is carried out over four hours at such a rate that thediethyl ether is refluxed, while the reaction vessel is cooled with thedry ice-isopropanol bath at 20C. When the addition is complete theresulting reaction mass is refluxed for 30 minutes, and 2520 g oftriethyl orthoformate is added over 1 /2 hours.

The reaction mass is then refluxed for seven hours. The reflux condenseris thereupon replaced by a distillation head and seven liters of diethylether is removed from the reaction mass until the pot temperature is C.The resulting thick slurry is cooled to 25C and five liters of a 6percent aqueous hydrochloric acid solution is slowly added whilemaintaining a pot tempera ture of 3040C.

The resulting acidic solution is transferred to a 5- gallon separatoryfunnel and the lower aqueous phase is removed. The upper organic phaseis extracted with 5 percent aqueous sodium bicarbonate solution untilthe organic phase has a neutral pH. The organic phase is then dried overanhydrous sodium sulfate and placed in a 3-liter distillation apparatus.The material is fractionated and the 1,1-diethoxy-3-butene product isdistilled at 82C and mm Hg pressure.

EXAMPLE Xl Preparation of l l -Dieth0xy( 4-Methylthio )butane Atwo-liter, three-neck flask equipped with a magnetic stirrer, dry icecondenser, and thermometer and 450 W high pressure Hanovia UV lamp ischarged with 1083 g (7.52 moles) of l,ldiethoxy-3-butene (prepared bythe process of Example X).

The contents of the flask are cooled to 0C and 384 g (8 moles) ofmethanethiol is added. Using a dry iceisopropanol cooling bath as wellas a condenser, the temperature of the reaction mass is maintained at0C.

The UV light is directed at the flask for a period of 10 minutes, andthe temperature of the reaction mass is allowed to rise to +l0c at whichpoint the UV light is shut off. The reaction mixture is then cooled to-5C and the UV light is again turned on and the reaction mass is exposedto UV light for another 10 minutes, at which point the reactiontemperature rises to 40C. The UV light is then shut off and the reactionmass is cooled to 10C, whereupon the UV light is turned on for 10minutes and the temperature of the reaction mass is allowed to increaseto 60C. The UV light is then shut off, the reaction mass is cooled to0C, and an additional 50 grams of methanethiol is added. The UV light isthen turned on for another 10 minutes and the reaction mass temperatureis permitted to rise to 20C.

The reaction mass is then flash-evaporated under 100 mm Hg vacuum at atemperature of 30C to obtain 1443 g of1,1-diethoxy-4-(methylthio)butane. The structure is confirmed by IR, NMRand mass spectral analysis.

EXAMPLE Xll Preparation of 1 ,1-Diethoxy-4-( Methylthio)butane A 100 ml,two-neck quartz flask equipped with a dry ice condenser and nitrogenblanket is charged with 57.6 g (0.4 moles) of l,l-diethoxy13-butene and20 g (0.42 moles) of methyl mercaptan. The mixture is then cooled to 0Cwith an isopropanol-dry ice bath. The flask contents are irradiated withultra-violet light from a I-Ianovia UV lamp for 13 hours while the bathtemperature is maintained at to 40C.

The resulting product is distilled to obtain 66.6 g of 80 percent purel,1-diethoxy-4-(methylthio)-butane liquid boiling at 72 and 1.5 mm Hg.

EXAMPLE XIII Preparation of 4-(Methy1thio)butanal A 5-gallon separatoryfunnel fitted with a mechanical stirrer is charged with ten liters ofdistilled water, 300 ml of concentrated sulfuric acid, and 1400 g of1,1- diethoxy-4-(methylthio)butane (produced by the process of ExampleXI).

The ingredients are stirred in the separatory funnel at v a temperatureof 25C for a period of 2 hours.

The reaction mass is then extracted with three oneliter portions ofmethylene chloride. The methylene chloride layer is separated, driedover anhydrous sodium sulfate, and evaporated down by rotary evaporationusing a water aspirator to obtain 1 188 g of crude material. The crudeis then transferred to a two-liter distillaton unit and distilled at atemperature of 8082C at 20 mm Hg pressure to yield 660 g (75 percent oftheory) having a refractive index of 1.4785 at C. The structure isconfirmed by IR, NMR and mass spectral analysis.

EXAMPLE XIV Use of 4-(Methylthi0)butanol 4-(Methy1thio)butano1 is addedto a commercially available tomato soup at the rate of 0.5 ppm andcompared by a bench panel (consisting of four people) with an unflavoredcontrol. It is concluded that the 4-(methy1thio)-butano1 adds a tomatopaste-character to the soup, increasing the intensity of the tomatotaste. The soup flavored with 4-(methylthio)butan0l is preferred.

EXAMPLE XV 4-(Methylthio)butano1 is added to a commercially availablemushroom soup at the rate of 1.0 ppm and compared by a bench panel(consisting of four individuals) with an unflavored control. The soupflavored with 4-(methylthio)-butano1 has a stronger mushroom aroma andtaste (masking the starch and flour notes present) and is preferred asbeing more mushroomlike.

EXAMPLE XVI Use of 4-( Methylthio)butanol 4-(Methy1thio)butana1 is addedto a commercially available tomato soup at the rate of 1 ppm. The4-(methy1thioJbutanal is found to add the aroma and taste of freshtomatoes to the soup, overcoming the flour and starch notes of the soup.

EXAMPLE XVII Use of Ethyl 4-( Methylthio)butyrate Ethyl4-(methylthio)butyrate is added to a cooked cheese sauce prepared byadmixing the following materials:

Ingredient Amount(grams) Hydrolyzed vegetable powder, Nestle 3.5 Cheddarcheese powder 1 1.5

Continued Ingredient Amount(grams) Corn starch 13.5 Monosodium glutamate6.5 Sodium citrate 1.0 Table salt 4.0 Whey 60.0

The butyrate is added at the rate of 0.5 ppm and 50 g of the formulationis added to 250 ml of milk and heated to boiling under continuousstirring. The cheese aroma is increased adding notes which are usuallypresent in surface-ripened cheese and also increasing the cheese flavorintensity.

EXAMPLE XVIII Use of Methyl 4-(Methylthio)butyrate One ppm methyl4-(methylthio)butyrate is added to beef broth prepared from a commercialdried mixture and 250 ml hot water. The methyl 4-(methy1thio)butyrateincreases the meat character and enhances the spice note. The resultantbeef broth has an improved more blended meaty flavor than does theunflavored beef broth.

EXAMPLE XIX Use of Methyl 4-(Methylthio)butyrate Methyl4-(methylthio)butyrate is added to a prepared New England clam chowderat the rate of 4 ppm (1 mg/250 ml). The sample to which the methyl4-(methylthio)butyrate is added has an enhanced fish flavor as comparedto a control to which no methyl 4-(methylthio)-butyrate is added.

EXAMPLE XX The following tobacco flavor is prepared:

The mixture is added to tobacco at the rate of 0.25 percent. The ethyl4-(methylthio)butyrate enchances the pineapple character of this fruityflavor for tobacco. The ethyl 4-(methylthio)butyrate also enables theacetaldehyde level to be raised tenfold as compared to the permissibleacetaldehyde levels in ordinary fruit flavors for tobacco.

EXAMPLE XXI The following perfume formulation is prepared:

Ingredient Amount( parts) Ethyl 4-(methy1thio)hutyratc 5.004Methylthio)hutanol 10.00 Benzyl alcohol 50.00 Benzyl acetate 100.00

The ethyl 4(methylthio)butyrate imparts a fruity, ylang jasmin note tothis floral essential oil composition. The 4-methylthio)butanol impartsa green celery jasmin note to this composition.

EXAMPLE XXII The following perfume formulation is prepared:

Ingredient Amunt(parts) l, l-Diethoxy-4-(methylthio )butune 3.00 Methyl4-(mcthylthio)hutyrate 10.00 4-( Methylthio )butanol 5.00 Hexyl cinnamicaldehyde 20.00

-C0nt1nued Benzyl acetate 10.00 4-( 4-Mcthyl-4-hydroxyamyl)cyclohex-3-ene carboxaldehydc 5.00 Benzyl benzoate 15.00 Linalool 50.00Eugenol 5.00 Linalyl acetate 60.00 Indol 1.00 Benzyl alcohol 10.00Tcrpeneol 3.00 Sandalwood oil 1.00

The l,1-diethoxy-4-(methylthio)butane imparts a green, galbanum note tothis floral type essential oil formulation. The methyl4-(methylthio)butyrate imparts a sweet ylang note. The4-(methylthio)butanal imparts a green jasmin character to the overallfloral character.

What is claimed is:

1. A method for altering the fragrance properties of a perfumecomposition which comprises adding a fragrance effecting amount of a4-(methylthio) butane derivative having the formula CH s (CH2) 3 c H.

Page 1 of 2 UNITED STATES PATENT @FFICE CERTIFICATE OF CORRECTIONPATENTNO. 3,904,556

DATED September 9, 1975 INVENTOMS), ALAN O. PITTET, JOHN V. PASCALE,

' STUART PATTON and MICHAEL H. BRODNITZHiscmflfiedmatmmrammaminmeamwe-memfimdpmemandflmtsmdLefimsPammamhmwymnmmdasmwnmmw Col. 2, lines 4 and 14, correct the spelling of"alko y" line 13, correct the spelling of "embodiments" line 37, correctthe spelling of "tomato" line 54, correct the spelling of "compositions"Coll 3, line 12, delete "the" (first occurrence) and substitute in lieuthereof, -and line 14, after "well" and before "as", insert productsline19, delete the word "as" after "such" line 27, "conditions" should read-conditioners line 50, after "starch" and before "notes" insert--flavorline 62, correct the spelling of "isobutylthiazole" Col. 4, line22, correct the spelling of "hydrogen" line 36, correct the spelling of"and" line 39, "l(methylthio(butane" should read 4-(methylthio)butane--PATENT NO.

DATED INVENTOR(S) I Page 2 Of 2 UNITED STATES PATENT QFFICE CERTIFICATEOF CORRECTION It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below:

[SEAL] 5, line 1, insert a space between "are" and "used" 7, line 28,correct the spelling of "about" 8, line 54, "(u.l04" should read (O.l04-

9, line 5, change "butane" to -butanal-- line 66, "deithyl" should read--diethyl- 13, line 50, Example XVI, in the title "butanol" should read-butanal- Signed and Sealed this Sixth Day of July 1976 A nest:

RUTH C. MASON Arresting Officer C. MARSHALL DANN Commissioner vflalenlsand Trademarks

1. A METHOD FOR ALTERING THE FRAGRANCE PROPERTIES OF A PERFUMECOMPOSITION WHICH COMPRISES ADDING A FRAGRANCE EFFECTING AMOUNT OF A4-(METHYLTHIO) BUTANE DERIVATIVE HAVING THE FORMULA